A “defend–attack and capture flag” strategy for cascade management of hepatic ischemia reperfusion injury

• Published in: Chemical engineering journal (Lausanne, Switzerland : 1996) Vol. 487; p. 150501
• Main Authors: Zhang, Wenze, Shen, Zhuoxia, Li, Chaoran, Yang, Yumeng, Zhang, Tiange, Yu, Bo-Yang, Zheng, Xianchuang, Tian, Jiangwei
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.05.2024
• Subjects: Hepatic ischemia reperfusion injury; Hypoxia; Photoacoustic imaging; Photothermal preprotection; Wedelolactone; Wedelolactone; Hypoxia; Photoacoustic imaging; Photothermal preprotection; Hepatic ischemia reperfusion injury
• ISSN: 1385-8947; 1873-3212
• DOI: 10.1016/j.cej.2024.150501

•The first example of exploiting photothermal preprotection to defend HIRI.•Wedelolactone can serve as a new and effective drug for the treatment of HIRI.•Hypoxia dynamics in HIRI was studied by photoacoustic imaging for the first time.•Hypoxia can serve as an indicator for monitoring the treatment outcome of HIRI. Hepatic ischemia reperfusion injury (HIRI) following transplantation or resection can lead to irreversible liver dysfunction and even failure, yet current therapeutic interventions are limited. Herein, we introduce a “defend–attack and capture flag” nanotheranostic strategy for the cascade management of HIRI. Firstly, the NIR-II photothermal pretreatment with the developed nanosystem provides preprotection for the liver, acting as “defend”. Subsequently, the pharmacotherapy furnishes direct cure for HIRI via the delivery and controlled release of wedelolactone from the nanosystem, serving as “attack”. Meanwhile, the photoacoustic (PA) imaging ability of the nanosystem enables the real-time monitoring of the inflammatory hypoxia, which is the “flag” to be captured in HIRI treatment. The photothermal preprotection can activate heat shock factor 1 (HSF-1), while the pharmaceutical therapy directly attacks NF-κB, both of which eventually inhibits NLRP3 inflammasome, thus reducing the activity of proinflammatory cytokine IL-1β, ending up with the alleviation of necrosis and apoptosis in HIRI. Such treatment effect can be reported by the real-time PA imaging. By the organic combination of the above three-step mechanism, significantly enhanced therapeutic efficacy was achieved in the animal model of HIRI, providing an effective solution for overcoming the challenge of HIRI.